Analysis of the role of hematopoietic stem-cell transplantation in infants with acute lymphoblastic leukemia in first remission and MLL gene rearrangements: a report from the Children's Oncology Group

Abstract

Purpose: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with current therapy, the event-free survival (EFS) of infants with ALL, particularly those with mixed lineage leukemia (MLL) gene rearrangements, is only 30% to 40%. Relapse has been the major source of treatment failure for these patients. The parallel Children's Cancer Group (CCG) 1953 and Pediatric Oncology Group (POG) 9407 studies were designed to test the hypothesis that more intensive therapy, including dose intensification of chemotherapy, and hematopoietic stem-cell transplantation (HSCT) would improve the outcome for this group of patients.

Patients and methods: One hundred eighty-nine infants (CCG 1953, n = 115; POG 9407, n = 74) were enrolled between October 1996 and August 2000. For infants with the MLL gene rearrangement and an appropriate donor, HSCT was the preferred treatment on CCG 1953 and investigator option on POG 9407 after completion of the second phase of therapy. Fifty-three infants underwent HSCT.

Results: The 5-year EFS rate was 48.8% (95% CI, 33.9% to 63.7%) in patients who received HSCT and 48.7% (95% CI, 33.8% to 63.6%) in patients treated with chemotherapy alone (P = .60). Transplantation outcomes were not affected by the preparatory regimen or donor source.

Conclusion: Our data suggest that routine use of HSCT for infants with MLL-rearranged ALL is not indicated. However, limited by small numbers, this study should not be considered the definitive answer to this question.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

CONSORT diagram. Eligibility and assignment of patients: Children's Cancer Group 1953 and Pediatric Oncology Group 9407. SCT, stem-cell transplantation; PI, principal investigator; MLL, mixed lineage leukemia; chemo, chemotherapy; EFS, event-free survival.

Fig 2.

(A) Event-free survival (EFS) comparing on- and off-study remission bone marrow transplantation (RBMT) groups versus control chemotherapy group (MLL-positive subset only). (*) Baseline time for RBMT patients is from date of bone marrow transplantation (BMT); for control chemotherapy patients, baseline time is from the median time to transplantation, which was 143 days from study entry. (B) EFS comparing on-study remission hematopoietic stem-cell transplantation (HSCT) group, off-study remission HSCT group, and chemotherapy control group (MLL-positive subset only). (†) Baseline time for remission HSCT patients is from date of HSCT; for control chemotherapy patients, baseline time is from the median time to transplantation, which was 177 days from study entry. (C) EFS outcome for RBMT by total-body irradiation (TBI) status (MLL-positive subset only). (‡) Baseline time for RBMT patients is from date of BMT. (D) EFS outcome for RBMT by donor type (MLL-positive subset only). (§) Baseline time for RBMT patients is from date of BMT. RHR, relative hazard rate.